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Biomedical subjects

J Richards

Publications and source records attributed to J Richards.

At least 73 records · Page 4Linked to original sources

Rapid pathogen detection using a microchip PCR array instrument.

An array of PCR microchips for rapid, parallel testing of samples for pathogenic microbes is described. The instrument, called the Advanced Nucleic Acid Analyzer (ANAA), utilizes 10 silicon reaction chambers with thin-film resistive heaters and solid-state optics. Features of the system include efficient heating and real-time monitoring, low power requirements for battery operation, and no moving parts for reliability and ruggedness. We analyzed cultures of Erwinia herbicola vegetative cells, Bacillus subtilis spores, and MS2 virions, which simulated pathogenic microbes such as Yersinia pestis, Bacillus anthracis spores, and Venezuelan equine encephalitis, respectively. Detection of microbes was achieved in as little as 16 min with detection limits of 10(5)-10(7) organisms/L (10(2)-10(4) organisms/mL).

Bacillus subtilis↗

Stress at work.

Explore the source record for details and available documents.

Burnout, Professional↗

BIMT 17: a putative antidepressant with a fast onset of action?

BIMT 17, the only compound reported to be a full 5-HT1A agonist and a 5-HT2A antagonist at the frontal cortex, was assessed in three animal paradigms sensitive to antidepressants in rats: olfactory bulbectomy (OB), differential-reinforcement-of-low rate 72-s (DRL 72-s) and learned helplessness (LH). In the OB rats, BIMT 17, given once daily for 14 consecutive days at an i.p. dose of 10 mg/kg, but not of 20 mg/kg, reduced the increase in ambulation of OB rats, 24 h after the last administration. In the DRL 72-s test, BIMT 17 had a different profile than imipramine. A single i.p. injection of 5, 10, 15 or 20 mg/kg BIMT 17, in contrast to the same doses of imipramine, did not affect response and reinforcement rate in DRL 72-s 1 h after the administration. On the other hand, BIMT 17 slightly shifted the peak of the interresponse time (IRT) distribution towards shorter IRT duration, while imipramine shifted the peak of the IRT distribution towards longer IRT duration. In the LH test, acute oral doses (36, 48 or 60 mg/kg) of BIMT 17, given 30 min before testing, reduced the number of escape failures in LH without altering the intertrial crossings. This effect was also induced by a repeated, but not single, administration with 8 or 16 mg/kg imipramine. The plasma levels following i.p. 10 or oral 48 mg/kg BIMT 17 were in the same range. These results indicate that BIMT 17 does not behave like imipramine in all the tests, and suggest that BIMT 17 acts through different mechanisms of action than imipramine. Only clinical trials will tell whether these mechanisms will be relevant, but if so, BIMT 17 might induce a faster onset of therapeutic activity.

Animals↗

Health-related behaviours and psycho-social characteristics of 18 year-old Australians.

Psychosocial variables associated with health-related behaviours for diet, physical activity, alcohol consumption and smoking were examined in 18 year-old Australian men (n = 301) and women (n = 282). These psychosocial variables included Type A behaviour and depression, perceived self-efficacy for engaging in healthy behaviours and perceived barriers to performing these behaviours. Self-efficacy for following a healthy diet and moderating alcohol intake was greater in females but males had higher self-efficacy for physical activity. Self-efficacy for smoking did not differ according to gender. Lack of willpower was perceived as a barrier to desirable dietary, smoking and physical activity behaviours. Other perceived diet-related barriers included buying suitable foods when eating out, ignorance about appropriate foods and, in young women, perceived expense. Barriers for desirable levels of physical activity included planning time, tiredness, limiting social life and lack of social support. Social occasions were the main perceived barriers preventing both alcohol moderation and quitting smoking. Lack of family support, stress and concerns about weight gain, particularly in women, were perceived barriers to smoking cessation. Type A behaviour was associated with smoking and "unsafe" drinking in both men and women, generally unhealthy dietary choices in young women but with greater physical activity in young men. Depressive affect was significantly higher in female smokers and "unsafe" drinkers and tended to have an inverse relationship with physical activity in men and women. Depressive affect was inversely related to self-efficacy in both men and women for each of the health behaviours examined. Health promotion in young adults should therefore attempt to increase self-efficacy and address perceived barriers to change, taking into account gender-related differences in attitudes and the influence of depression and Type A characteristics on health-related behaviours.

Adolescent↗

Effects of varying levels of positive end-expiratory pressure on intracranial pressure and cerebral perfusion pressure.

OBJECTIVE: To determine the influence of positive end-expiratory pressure (PEEP) on intracranial pressure and cerebral perfusion pressure. DESIGN: Neurosurgical intensive care patients requiring intracranial pressure monitoring and mechanical ventilation were studied in a randomized, controlled study. SETTING: Tertiary care, neurosurgical intensive care unit. PATIENTS: Eighteen patients were enrolled in the study. Patients had posttraumatic head injuries (n = 9), subarachnoid hemorrhage (n = 7), obstructive hydrocephalus (n = 1), and intracerebral hemorrhage of unknown cause (n = 1). INTERVENTIONS: Patients had PEEP levels of 5, 10, and 15 cm H2O applied to their lungs. MEASUREMENTS AND MAIN RESULTS: Changes in intracranial pressure, mean arterial pressure, and cerebral perfusion pressure were measured. The results were analyzed separately for patients with normal and increased intracranial pressure (> 15 mm Hg). PEEP at 5 cm H2O had no effect on intracranial pressure in the group with normal intracranial pressure. However, PEEP at 10 and 15 cm H2O produced a significant (p < .05) increase in intracranial pressure (1.9 and 1.5 mm Hg, respectively). In the group with increased intracranial pressure, no significant change in intracranial pressure occurred at any of the PEEP levels used. In both groups, cerebral perfusion pressure was unchanged throughout. CONCLUSIONS: In patients with normal intracranial pressure, PEEP at 5 cm H2O did not significantly alter intracranial pressure. The clinical relevance of the intracranial pressure increase at PEEP levels of 10 and 15 cm H2O is questionable because cerebral perfusion pressure did not change and remained > 60 mm Hg. In patients with increased intracranial pressure, higher levels of PEEP did not significantly change intracranial pressure or cerebral perfusion pressure.

Adult↗

Characteristics of the new long-stay population in an inner Melbourne acute psychiatric hospital.

OBJECTIVE: There has been an accumulation of so-called 'new long-stay' (NLS) patients in psychiatric hospitals. To date, no Australian studies have characterised this patient group. We aimed to study the demography, and clinical and social functioning of the NLS population at Royal Park Hospital (RPH) together with patients' attitudes to treatment and views on future placement. METHOD: All 30 NLS patients at RPH were identified. Twenty-seven consenting patients were assessed using the following standardised instruments: Manchester Scale for psychopathology, Life Skills Profile (LSP), Physical Health Index and Patient Attitude Questionnaire. Information on past psychiatric history, past treatment and current treatment was collected. Insight and compliance were assessed. RESULTS: The majority of patients were single men with a diagnosis of schizophrenia. Forty-one percent were detained in hospital involuntarily and 56% were considered dangerous to themselves or others. The patients were characterised by high levels of positive and negative symptoms. They were most impaired with respect to 'social contact' relative to the other subscales of the LSP. While 10 (48%) patients expressed a desire to leave hospital, only one patient considered that anyone would cohabit with them. Over two-thirds considered they had been unwell and that medication had helped. Staff rated one-third as having major problems with compliance. About two-thirds of patients had disability secondary to comorbid physical illnesses. CONCLUSION: Like other NLS patients studied in the United Kingdom and Ireland, this group had significant handicaps secondary to psychiatric illness, concomitant physical illness and disability and behaviour unacceptable in community settings. They were also characterised by significant social isolation. These factors may be important determinants of rehabilitation failure and need to be addressed in the process of de-institutionalisation as well as in longitudinal studies examining these and other factors predicting NLS status.

Activities of Daily Living↗

Phosphatidic acid mobilized by phospholipase D is involved in the phorbol 12-myristate 13-acetate-induced G2 delay of A431 cells.

This study was aimed at gaining an understanding of metabolic events responsible for the inhibition of cells in G2 phase, a known physiological restriction site in the cell cycle of multicellular organisms. In an earlier study, phosphatidic acid was proposed as an inhibitory mediator in the epidermal growth factor (EGF)-induced inhibition of A431 cells in G2 phase via the phospholipase C pathway [Kaszkin, Richards and Kinzel (1992) Cancer Res. 52, 5627-5634]. We show here that the phorbol ester phorbol 12-myristate 13-acetate (PMA) induces a reversible inhibition of the G2/M transition in A431 cells under conditions of phospholipase D-catalysed phosphatidic acid formation. Such PMA-induced inhibition in G2 phase is largely attenuated in the presence of 1-propanol (but not of 2-propanol). In this case the amount of phosphatidic acid is reduced to almost control levels, and instead phosphatidylpropanol is formed. In the case of EGF-induced activation of a phospholipase D the amount of phosphatidic acid is only slightly decreased in the presence of a primary alcohol. Under these conditions the EGF-induced G2 delay was not affected. The correlation between the formation of phosphatidic acid and the G2 delay induced by PMA, as well as by an exogenous bacterial phospholipase D (from Streptomyces chromofuscus), could be supported by using synchronized cells in order to increase the population of cells in G2 phase. This study indicates that the formation of substantial amounts of phosphatidic acid immediately before entry into mitosis seems to be important for establishing a delay in the cell cycle at the G2/M border by exogenous ligands.

1-Propanol↗

Role of cdc25-C phosphatase in the immediate G2 delay induced by the exogenous factors epidermal growth factor and phorbolester.

Studies on the link between cellular signalling and cell cycle control at the G2 checkpoint have shown that, in HeLa cells, epidermal growth factor (EGF) and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) rapidly inhibit the G2-M transition by preventing the key component of mitosis-promoting factor (MPF), p34cdc2, from expressing protein kinase activity. The kinase activity of active MPF is not inhibited; rather, the conversion of pre-MPF to MPF, i.e., the activating dephosphorylation of p34cdc2, at tyrosine is rapidly blocked (Barth and Kinzel, 1994, Exp. Cell Res. 212:383-388; 1995, J. Cell. Physiol., 162:44-51). The phosphatase responsible, cdc25-C, is activated by phosphorylation in mitotic cells starting at the G2-M transition in an autocatalytic loop with MPF (Hoffmann et al., 1993, EMBO J. 12:53-63). We now show that, concomitant with the prevention of MPF activation, EGF and TPA induced a reduction of the activity of cdc25-C in synchronized cultures. Furthermore, treatment of mitotic HeLa cells with TPA did not influence the kinase activity of MPF but caused a rapid decrease of the specific enzyme activity of cdc25-C, probably due to dephosphorylation of the enzyme, as indicated by reduced binding of monoclonal MPM-2 antibody specific for phosphoepitopes in M phase. Because of its inability to induce signalling during division, EGF failed to influence the activity of cdc25-C in mitotic cells. The scenario in cells late in G2 that are committed to enter mitosis may be as follows: In those cells where the signalling pathways responding to EGF as well as those responding to TPA are still open, cdc25-C is prevented by dephosphorylation from exceeding the threshold level of activity required to initiate the activation of and the autocatalytic feedback loop with p34cdc2 and to enter mitosis. Therefore, cdc25-C appears to represent part of an interface between cellular signalling and cell cycle control in G2 phase.

CDC2 Protein Kinase↗

Comparison of a microtitration plate ELISA with a standard cultural procedure for the detection of Salmonella spp. in chicken.

A rapid antibody-capture enzyme-linked immunosorbent assay (ELISA) detecting a wide range of Salmonella serotypes and employing only one culture stage was used to analyze the giblets and body cavity rinsings from frozen chickens. The results from the ELISA were compared with those obtained using a standard cultural procedure in current use in two laboratories, Norwich (N) and Ipswich (I), of the Public Health Laboratory Service (PHLS) in the UK. ELISAs were carried out on the same samples at each of two PHLS laboratories and at the Institute of Food Research with good agreement (94% and 90%). When compared with the cultural method there was 80% and 70% agreement with the ELISA with the PHLS(N) and PHLS(I) samples. The ELISA appeared to have a false-positive rate of 17% (samples from PHLS(N)) but on reculture of the "negative" samples this rate fell to 7%. The false-negative rate for the ELISA was 26% (samples from PHLS(N)) which appeared to be due to insufficient growth of the Salmonella spp. in the single cultural step employed in the ELISA rather than lack of recognition by the antibodies. The problem of false negatives with the cultural method is also discussed. These results are comparable to previously published studies relating immunoassays and the conventional procedure for Salmonella detection when analyzing similar samples. Suggestions are made as to how further increases in ELISA efficiency might be brought about.

Animals↗

Methylenedioxymethamphetamine-induced serotonin deficits are followed by partial recovery over a 52-week period. Part II: Radioligand binding and autoradiography studies.

In our study, age-matched Holtzman Sprague-Dawley rats (275-300 g) received injections with either saline (0.9%) or 3,4-methylenedioxymethamphetamine (MDMA; 20 mg/kg free base, s.c) twice daily for 4 days and allowed to recover for 2, 8, 16, 32 and 52 wk after the final injection before death. Radioligand binding studies with 125I-RTI-55 to dopamine uptake sites in striatal homogenates showed no effect of MDMA on the density of dopamine uptake sites. In contrast, saturation binding studies with 125I-RTI-55 to 5-HT uptake sites in hippocampal and frontal-parietal homogenates showed a significant reduction in the number of uptake sites at 2 wk after MDMA treatment (34 and 25%, respectively of controls). By 16 wk, a partial recovery in the number of 5-HT uptake sites was observed in both tissues; however, only a full recovery of serotonin uptake sites was observed in hippocampus at the end of 52 wk. In more detailed studies using autoradiography with 125I-RTI-55, recovery of serotonin uptake sites varied from region to region. In particular, recovery of 5-HT uptake sites in cerebral cortex was observed to follow a rostral-caudal gradient. In addition, recovery of 5-HT uptake site in hippocampus also followed a rostral-caudal gradient. Different rates of recovery of 5-HT uptake sites were also observed for cingulate cortex, laterodorsal thalamus and ventromedial hypothalamus. No effect of MDMA was observed over lateral hypothalamus, substantia nigra and ventral tegmental area, or over serotonergic cell bodies such as dorsal raphe and median raphe. In conclusion, our study is consistent with previous studies describing the selective neurotoxicity of MDMA for serotonin neurons and presents evidence showing the rate of recovery of 5-HT uptake sites varies according to region and that recovery of 5-HT uptake sites in neocortex and hippocampus follows a rostral-caudal gradient.

Animals↗

Radiologic study of the accuracy of a tibial intramedullary cutting guide for knee arthroplasty.

Twenty-one caucasian, adult cadaveric tibiae were prepared as for knee arthroplasty using an intramedullary cutting guide. The instrumentation was used to produce slots in the proximal tibia into which Kirschner wires were placed as radio-opaque markers for subsequent anteroposterior and lateral radiographs. The anatomic axis of the tibia and lines perpendicular to the wire markers were drawn on the radiographs and the angle between the two lines was measured to assess the accuracy of the cuts. Seventy-one percent of the tibial cuts were found to be within 2 degrees of the anatomic axis on the anteroposterior radiograph (mean, 2.1 degrees), while on the lateral radiograph, 81% of the cuts were within 2 degrees (mean, 1.8 degrees). There was a significant tendency to position the bone cuts in varus (P < .05), although this did not correlate with varus or valgus deformity of the bones. There was no consistent tendency to anterior or posterior tilt on the lateral radiograph (P > .05). The results compare favorably with those obtained from a specialist unit using an extramedullary alignment system. The authors conclude that the tibial intramedullary guide can lead to preparation of the proximal tibia for knee arthroplasty as accurately as the conventional extramedullary system.

Adult↗

The use, efficacy and monitoring of artificial nutritional support in a teaching hospital.

The implementation of circulated guidelines has been audited, by assessing the extent to which nutritional goals were set and achieved and recording the levels of morbidity as a result of complications. Adults receiving artificial nutritional support were studied over a six month period. Nutritional assessment was used to determine adequacy of prescription and efficacy of the support. Energy requirements were retrospectively calculated and compared with prescriptions and actual intakes. Complications and interruptions to the regimens which resulted in lost feeding time were recorded, as were patient outcomes. Nutrient prescriptions were inadequate, delivery of prescriptions was incomplete and thus nutrient supply inadequate.

Aged↗

Vimentin and CP49/filensin form distinct networks in the lens which are independently modulated during lens fibre cell differentiation.

The cells of the eye lens contain the type III intermediate filament protein vimentin, as well as two other intermediate filament proteins, CP49 and filensin. These two proteins appear to be unique to the differentiated lens fibre cell. Immunoblotting and confocal microscopy were used to describe changes which occur in these three intermediate filament proteins and the networks they form during fibre cell differentiation and maturation. The vimentin network was present in both epithelial cells and some fibre cells. Fibre cells were vimentin positive up to a specific point 2-3 mm in from the lens capsule where the vimentin signal was drastically reduced. The CP49/filensin network was not present in the undifferentiated epithelial cells but emerged in the differentiating fibre cells. This latter network exhibited a principally plasma membrane localization in younger fibre cells but became more cytoplasmic in older fibre cells. This change also occurred at a distinct point in fibre cell differentiation, much earlier than the observed loss of the vimentin network. The subcellular changes in the distributions of these cytoskeletal networks were correlated to the loss of the fibre cell nucleus, another feature of fibre cell differentiation. No correlation was found to changes in the vimentin network but nuclear loss did coincide with changes in the CP49/filensin network. Concomitant with nuclear pyknosis, there were also changes in the nuclear lamina as well as infringement of the nuclear compartment by CP49, as shown by confocal microscopy. This study demonstrates vimentin and the CP49/filensin network to be independent in the lens but both networks undergo dramatic changes in subcellular distribution during the differentiation/maturation of the fibre cell. Only changes in the CP49/filensin network can be correlated to nuclear loss. Thus in the lens, unlike mammalian erythropoiesis which is also characterized by nuclear loss, the vimentin network does not appear linked to nuclear retention.

Animals↗

Subsyndromal ("mixed") anxiety--depression in primary care.

OBJECTIVE: To determine in primary care settings the prevalence, clinical characteristics, and functional status of patients who have anxious and depressive symptoms who did not meet diagnostic criteria for major mood and anxiety diagnoses. DESIGN: Patients were screened with the General Health Questionnaire and interviewed if they exceeded the cutoff score of 5. Also, one patient whose score was below the cutoff was interviewed for every two patients whose scores were above the cutoff. SETTING: Five primary care sites in the United States, France, and Australia. PATIENT: Two hundred sixty-seven patients presenting to their primary care physicians for general medical care and follow-up. METHODS: Structured diagnostic interviews were conducted and ratings of anxiety, depression, and functional impairment were obtained by trained interviewers. RESULTS: After adjustments for sampling, 5% of the patients had symptoms of anxiety, depression, and functional impairment, without meeting formal criteria for a major DSM-III-R mood or anxiety disorder. This was comparable to the prevalence of diagnosable DSM-III-R mood disorders but only one-fourth the prevalence of diagnosable anxiety disorders. These patients who had subsyndromal symptoms had rates of lifetime psychiatric disorders and prior psychiatric treatment comparable to those of patients meeting criteria for major mood and anxiety disorders. CONCLUSION: The comparable rates of symptomatic distress, functional impairment, and prior psychiatric illness and treatment suggest that patients with subsyndromal anxiety and depressive symptoms warrant clinical recognition and possibly specific treatment.

Anxiety↗